Thursday, November 28, 2024

Fat cells remember being bigger—and act like it e.g. the yo-yo effect of dieting

Good news! Yesterday, I blogged here how the fat cell size might be related to diabetes and how fat cell grow and become skinny again.

Apparently, the duration of obesity is also affecting the success of weight loss treatment suggesting an early as possible treatment.

"When a person gains weight, the number of fat-storing cells in their body doesn’t really change. Instead, each cell expands to store more fat within it, and in so doing changes the way it responds to and stores nutrients. New research suggests that even after substantial fat loss, these cells (called adipocytes) “remember” their larger selves—which may help explain why it can be difficult to maintain weight loss.

... leading to “yo-yo” fluctuations in weight. Researchers studying human tissues first observed gene expression differences between the adipocytes of people diagnosed with obesity and those from people who had never been diagnosed. These differences persisted in participants who had lost weight after bariatric surgery.

Follow-up experiments in mice revealed durable tweaks to gene expression in fat cells that occur during obesity; they persist long after the cells have shrunk again, especially if the cells spent more time in an obese state. These changes “ prepare the adipocyte to quickly regain weight once high calorie intake is resumed,” ...

It remains unclear just how long this memory persists , the team notes, so it may fade with enough time. ..."

From the abstract:
"Reducing body weight to improve metabolic health and related comorbidities is a primary goal in treating obesity. However, maintaining weight loss is a considerable challenge, especially as the body seems to retain an obesogenic memory that defends against body weight changes. Overcoming this barrier for long-term treatment success is difficult because the molecular mechanisms underpinning this phenomenon remain largely unknown. Here, by using single-nucleus RNA sequencing, we show that both human and mouse adipose tissues retain cellular transcriptional changes after appreciable weight loss. Furthermore, we find persistent obesity-induced alterations in the epigenome of mouse adipocytes that negatively affect their function and response to metabolic stimuli. Mice carrying this obesogenic memory show accelerated rebound weight gain, and the epigenetic memory can explain future transcriptional deregulation in adipocytes in response to further high-fat diet feeding.

In summary, our findings indicate the existence of an obesogenic memory, largely on the basis of stable epigenetic changes, in mouse adipocytes and probably other cell types. These changes seem to prime cells for pathological responses in an obesogenic environment, contributing to the problematic ‘yo-yo’ effect often seen with dieting. Targeting these changes in the future could improve long-term weight management and health outcomes."

ScienceAdvisor



Fig. 1: Human AT [adipose tissue] retains cellular transcriptional changes after BaS [bariatric surgery]-induced WL [weight loss].


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